{"gene":"TG_231870","gene_symbol":"PEX5","run_date":"2026-09-08T12:58:24","timeline":{"discoveries":[{"year":2018,"finding":"Toxoplasma gondii Pex5 expressed in Pex5-deleted Saccharomyces cerevisiae rescues the PTS1 protein import defect, demonstrating that TgPex5 is a functional peroxisomal targeting signal 1 (PTS1) import receptor.","method":"Complementation assay in Pex5-deleted yeast (Saccharomyces cerevisiae)","journal":"Genes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional rescue in a well-established heterologous system, single lab, supported by two orthogonal methods (yeast complementation + in vitro binding)","pmids":["30158461"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"The PTS1-binding domain of Toxoplasma gondii Pex5 interacts in vitro with a PTS1 ligand derived from the putatively peroxisome-localised Toxoplasma sterol carrier protein (SCP2), establishing a direct physical interaction between TgPex5 and a cargo PTS1 peptide.","method":"In vitro binding assay (recombinant protein interaction)","journal":"Genes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro binding assay, single lab, corroborated by functional yeast complementation data in the same study","pmids":["30158461"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"GFP bearing an enhanced PTS1 (ePTS1) signal localises to peroxisome-like bodies when expressed in Toxoplasma gondii, indicating that a PTS1-dependent import pathway is active in the parasite.","method":"Fluorescence microscopy of GFP-ePTS1 expressed in Toxoplasma gondii","journal":"Genes","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment in the organism, single lab, consistent with complementary functional data in the same study","pmids":["30158461"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Although Pex5 is clearly identifiable in coccidian genomes, canonical membrane-bound docking partners Pex13 and Pex14 are absent, indicating that a nonconventional peroxisomal protein import mechanism operates downstream of Pex5 in Toxoplasma gondii and related coccidia.","method":"Comparative genomic survey of apicomplexan genomes","journal":"Genes","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/bioinformatic genome survey; no direct experimental validation of the absence of Pex13/Pex14 function","pmids":["30158461"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Phylogenetic analysis of Pex5 as an essential peroxisomal import receptor marker supports the presence of peroxisomes in Toxoplasma gondii and related genera, contradicting earlier claims that apicomplexans lack peroxisomes.","method":"Comparative genomics and phylogenetic analysis","journal":"Genome Biology and Evolution","confidence":"Low","confidence_rationale":"Tier 4 / Moderate — comparative genomic and phylogenetic inference across multiple alveolate species; no direct functional experiment on TgPex5 itself","pmids":["29202176"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"Toxoplasma gondii Pex5 is a functional PTS1 import receptor that binds PTS1-containing cargo proteins (including the SCP2 PTS1 ligand) in the cytosol and mediates their import into peroxisome-like organelles, but operates via a nonconventional membrane translocation mechanism because the canonical docking partners Pex13 and Pex14 are absent from the coccidian genome."},"narrative":{"mechanistic_narrative":"Toxoplasma gondii Pex5 is a functional peroxisomal targeting signal 1 (PTS1) import receptor that mediates cargo delivery into peroxisome-like organelles in the parasite [PMID:30158461]. TgPex5 expressed in Pex5-deleted Saccharomyces cerevisiae rescues the PTS1 import defect, establishing that it retains bona fide receptor activity [PMID:30158461], and its PTS1-binding domain physically engages a PTS1 ligand derived from the parasite sterol carrier protein SCP2, defining a direct receptor-cargo interaction [PMID:30158461]. Consistent with an active receptor, GFP bearing an enhanced PTS1 signal localizes to peroxisome-like bodies when expressed in T. gondii, demonstrating a functional PTS1-dependent import pathway in the parasite [PMID:30158461]. Beyond cargo recognition, the mechanism of membrane translocation downstream of TgPex5 has not been characterized in the available corpus.","teleology":[{"year":2018,"claim":"It was unknown whether Toxoplasma encoded a functional PTS1 import receptor; heterologous complementation established TgPex5 as a bona fide receptor rather than a mere sequence homolog.","evidence":"Complementation of Pex5-deleted S. cerevisiae by TgPex5, restoring PTS1 protein import","pmids":["30158461"],"confidence":"Medium","gaps":["Receptor activity shown only in a heterologous yeast system, not by direct loss-of-function in the parasite","Cargo repertoire imported by TgPex5 in vivo not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"To connect receptor activity to a physiological cargo, the PTS1-binding domain of TgPex5 was shown to bind a PTS1 ligand from the parasite SCP2, providing a direct receptor-cargo interaction.","evidence":"In vitro binding assay with recombinant TgPex5 PTS1-binding domain and an SCP2-derived PTS1 peptide","pmids":["30158461"],"confidence":"Medium","gaps":["Binding shown with a peptide ligand rather than full-length native SCP2","Peroxisomal localization of SCP2 in vivo not demonstrated","Affinity and specificity relative to other PTS1 cargo not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"To show the import pathway is operational in the organism itself, a reporter carrying an enhanced PTS1 signal was tracked in the parasite, revealing PTS1-dependent targeting to peroxisome-like bodies.","evidence":"Fluorescence microscopy of GFP-ePTS1 expressed in T. gondii","pmids":["30158461"],"confidence":"Medium","gaps":["Does not directly demonstrate TgPex5 dependence of the observed targeting","Nature and biogenesis of the peroxisome-like bodies not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"Comparative genomics addressed how import proceeds after cargo capture, finding that the canonical docking partners Pex13 and Pex14 are absent from coccidian genomes, implying a nonconventional translocation mechanism downstream of Pex5.","evidence":"Comparative genomic survey of apicomplexan genomes","pmids":["30158461"],"confidence":"Low","gaps":["Absence is inferred bioinformatically without experimental validation of Pex13/Pex14 function loss","The alternative docking/translocation machinery is unidentified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"Broader phylogenetic analysis used Pex5 as a peroxisome marker to argue that apicomplexans possess peroxisomes, contradicting prior claims that these organelles are absent.","evidence":"Comparative genomics and phylogenetic analysis across alveolate species","pmids":["29202176"],"confidence":"Low","gaps":["Inference from marker presence rather than direct functional characterization of TgPex5","Does not establish the full peroxisomal proteome or organelle physiology in T. gondii"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The membrane translocation machinery operating downstream of TgPex5 in the absence of Pex13/Pex14, and the in vivo essentiality and full cargo repertoire of TgPex5, remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No identification of the nonconventional docking/translocation factors","No direct parasite loss-of-function characterization of TgPex5","Full set of PTS1 cargo proteins undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["SCP2 (STEROL CARRIER PROTEIN, PTS1 CARGO LIGAND)"],"other_free_text":["Canonical peroxisomal docking partners Pex13 and Pex14 are absent from coccidian genomes, implying a nonconventional import mechanism downstream of TgPex5 [#3].","Functional PTS1 receptor activity demonstrated by heterologous rescue in Pex5-deleted S. cerevisiae [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"29202176","id":"PMC_29202176","title":"Distribution and Evolution of Peroxisomes in Alveolates (Apicomplexa, Dinoflagellates, Ciliates).","date":"2018","source":"Genome biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/29202176","citation_count":17,"is_preprint":false},{"pmid":"30158461","id":"PMC_30158461","title":"Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii.","date":"2018","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/30158461","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3550,"output_tokens":1259,"usd":0.014767,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6224,"output_tokens":2393,"usd":0.045472,"stage2_stop_reason":"end_turn"},"total_usd":0.060239,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"Toxoplasma gondii Pex5 expressed in Pex5-deleted Saccharomyces cerevisiae rescues the PTS1 protein import defect, demonstrating that TgPex5 is a functional peroxisomal targeting signal 1 (PTS1) import receptor.\",\n      \"method\": \"Complementation assay in Pex5-deleted yeast (Saccharomyces cerevisiae)\",\n      \"journal\": \"Genes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional rescue in a well-established heterologous system, single lab, supported by two orthogonal methods (yeast complementation + in vitro binding)\",\n      \"pmids\": [\"30158461\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The PTS1-binding domain of Toxoplasma gondii Pex5 interacts in vitro with a PTS1 ligand derived from the putatively peroxisome-localised Toxoplasma sterol carrier protein (SCP2), establishing a direct physical interaction between TgPex5 and a cargo PTS1 peptide.\",\n      \"method\": \"In vitro binding assay (recombinant protein interaction)\",\n      \"journal\": \"Genes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro binding assay, single lab, corroborated by functional yeast complementation data in the same study\",\n      \"pmids\": [\"30158461\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"GFP bearing an enhanced PTS1 (ePTS1) signal localises to peroxisome-like bodies when expressed in Toxoplasma gondii, indicating that a PTS1-dependent import pathway is active in the parasite.\",\n      \"method\": \"Fluorescence microscopy of GFP-ePTS1 expressed in Toxoplasma gondii\",\n      \"journal\": \"Genes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment in the organism, single lab, consistent with complementary functional data in the same study\",\n      \"pmids\": [\"30158461\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Although Pex5 is clearly identifiable in coccidian genomes, canonical membrane-bound docking partners Pex13 and Pex14 are absent, indicating that a nonconventional peroxisomal protein import mechanism operates downstream of Pex5 in Toxoplasma gondii and related coccidia.\",\n      \"method\": \"Comparative genomic survey of apicomplexan genomes\",\n      \"journal\": \"Genes\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/bioinformatic genome survey; no direct experimental validation of the absence of Pex13/Pex14 function\",\n      \"pmids\": [\"30158461\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Phylogenetic analysis of Pex5 as an essential peroxisomal import receptor marker supports the presence of peroxisomes in Toxoplasma gondii and related genera, contradicting earlier claims that apicomplexans lack peroxisomes.\",\n      \"method\": \"Comparative genomics and phylogenetic analysis\",\n      \"journal\": \"Genome Biology and Evolution\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Moderate — comparative genomic and phylogenetic inference across multiple alveolate species; no direct functional experiment on TgPex5 itself\",\n      \"pmids\": [\"29202176\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"Toxoplasma gondii Pex5 is a functional PTS1 import receptor that binds PTS1-containing cargo proteins (including the SCP2 PTS1 ligand) in the cytosol and mediates their import into peroxisome-like organelles, but operates via a nonconventional membrane translocation mechanism because the canonical docking partners Pex13 and Pex14 are absent from the coccidian genome.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"Toxoplasma gondii Pex5 is a functional peroxisomal targeting signal 1 (PTS1) import receptor that mediates cargo delivery into peroxisome-like organelles in the parasite [#0]. TgPex5 expressed in Pex5-deleted Saccharomyces cerevisiae rescues the PTS1 import defect, establishing that it retains bona fide receptor activity [#0], and its PTS1-binding domain physically engages a PTS1 ligand derived from the parasite sterol carrier protein SCP2, defining a direct receptor-cargo interaction [#1]. Consistent with an active receptor, GFP bearing an enhanced PTS1 signal localizes to peroxisome-like bodies when expressed in T. gondii, demonstrating a functional PTS1-dependent import pathway in the parasite [#2]. Beyond cargo recognition, the mechanism of membrane translocation downstream of TgPex5 has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"It was unknown whether Toxoplasma encoded a functional PTS1 import receptor; heterologous complementation established TgPex5 as a bona fide receptor rather than a mere sequence homolog.\",\n      \"evidence\": \"Complementation of Pex5-deleted S. cerevisiae by TgPex5, restoring PTS1 protein import\",\n      \"pmids\": [\"30158461\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Receptor activity shown only in a heterologous yeast system, not by direct loss-of-function in the parasite\",\n        \"Cargo repertoire imported by TgPex5 in vivo not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To connect receptor activity to a physiological cargo, the PTS1-binding domain of TgPex5 was shown to bind a PTS1 ligand from the parasite SCP2, providing a direct receptor-cargo interaction.\",\n      \"evidence\": \"In vitro binding assay with recombinant TgPex5 PTS1-binding domain and an SCP2-derived PTS1 peptide\",\n      \"pmids\": [\"30158461\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding shown with a peptide ligand rather than full-length native SCP2\",\n        \"Peroxisomal localization of SCP2 in vivo not demonstrated\",\n        \"Affinity and specificity relative to other PTS1 cargo not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To show the import pathway is operational in the organism itself, a reporter carrying an enhanced PTS1 signal was tracked in the parasite, revealing PTS1-dependent targeting to peroxisome-like bodies.\",\n      \"evidence\": \"Fluorescence microscopy of GFP-ePTS1 expressed in T. gondii\",\n      \"pmids\": [\"30158461\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not directly demonstrate TgPex5 dependence of the observed targeting\",\n        \"Nature and biogenesis of the peroxisome-like bodies not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Comparative genomics addressed how import proceeds after cargo capture, finding that the canonical docking partners Pex13 and Pex14 are absent from coccidian genomes, implying a nonconventional translocation mechanism downstream of Pex5.\",\n      \"evidence\": \"Comparative genomic survey of apicomplexan genomes\",\n      \"pmids\": [\"30158461\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Absence is inferred bioinformatically without experimental validation of Pex13/Pex14 function loss\",\n        \"The alternative docking/translocation machinery is unidentified\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Broader phylogenetic analysis used Pex5 as a peroxisome marker to argue that apicomplexans possess peroxisomes, contradicting prior claims that these organelles are absent.\",\n      \"evidence\": \"Comparative genomics and phylogenetic analysis across alveolate species\",\n      \"pmids\": [\"29202176\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Inference from marker presence rather than direct functional characterization of TgPex5\",\n        \"Does not establish the full peroxisomal proteome or organelle physiology in T. gondii\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The membrane translocation machinery operating downstream of TgPex5 in the absence of Pex13/Pex14, and the in vivo essentiality and full cargo repertoire of TgPex5, remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No identification of the nonconventional docking/translocation factors\",\n        \"No direct parasite loss-of-function characterization of TgPex5\",\n        \"Full set of PTS1 cargo proteins undefined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005052\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005777\", \"supporting_discovery_ids\": [2, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016558\", \"supporting_discovery_ids\": [0, 2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SCP2 (sterol carrier protein, PTS1 cargo ligand)\"],\n    \"other_free_text\": [\n      \"Canonical peroxisomal docking partners Pex13 and Pex14 are absent from coccidian genomes, implying a nonconventional import mechanism downstream of TgPex5 [#3].\",\n      \"Functional PTS1 receptor activity demonstrated by heterologous rescue in Pex5-deleted S. cerevisiae [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_231870","name":"PEX5","product":"peroxisome biogenesis protein PEX5","uniprot_acc":"S8GAU8","chromosome":"TGME49_chrVIII","start_pos":1595793},{"strain":"GT1","gene_id":"TGGT1_231870","name":null,"product":"tetratricopeptide repeat-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":1592444},{"strain":"RH88","gene_id":"TGRH88_075940","name":null,"product":"tetratricopeptide repeat-containing protein","uniprot_acc":null,"chromosome":"CM023089","start_pos":6703222},{"strain":"VEG","gene_id":"TGVEG_231870","name":null,"product":"tetratricopeptide repeat-containing protein","uniprot_acc":"A0A0F7V279","chromosome":"TGVEG_chrVIII","start_pos":1603253}]}